Clinical data | |
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Trade names | Velban, Velbe, others |
Other names | vincaleukoblastine |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682848 |
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Routes of administration | intravenous |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | n/a |
Metabolism | Liver (CYP3A4-mediated) |
Elimination half-life | 24.8 hours (terminal) |
Excretion | Bile duct and kidney |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.011.577 |
Chemical and physical data | |
Formula | C46H58N4O9 |
Molar mass | 810.989 g·mol−1 |
3D model (JSmol) | |
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Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. [1] This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer. [1] It is given by injection into a vein. [1]
Most people experience some side effects. [1] Commonly it causes a change in sensation, constipation, weakness, loss of appetite, and headaches. [1] Severe side effects include low blood cell counts and shortness of breath. [1] It should not be given to people who have a current bacterial infection. [1] Use during pregnancy will likely harm the baby. [1] Vinblastine works by blocking cell division. [1]
Vinblastine was isolated in 1958. [2] An example of a natural herbal remedy that has since been developed into a conventional medicine, vinblastine was originally obtained from the Madagascar periwinkle. [3] It is on the World Health Organization's List of Essential Medicines. [4]
Vinblastine is a component of a number of chemotherapy regimens, including ABVD for Hodgkin lymphoma. [5] It is also used to treat histiocytosis according to the established protocols of the Histiocytosis Association.
Adverse effects of vinblastine include hair loss, loss of white blood cells and blood platelets, gastrointestinal problems, high blood pressure, excessive sweating, depression, muscle cramps, vertigo and headaches. [6] [1] As a vesicant, vinblastine can cause extensive tissue damage and blistering if it escapes from the vein from improper administration. [7]
Vinblastine is a vinca alkaloid [8] [2] [9] and a chemical analogue of vincristine. [10] [11] It binds tubulin, thereby inhibiting the assembly of microtubules. [12] Vinblastine treatment causes M phase specific cell cycle arrest by disrupting microtubule assembly and proper formation of the mitotic spindle and the kinetochore, each of which are necessary for the separation of chromosomes during anaphase of mitosis. Toxicities include bone marrow suppression (which is dose-limiting), gastrointestinal toxicity, potent vesicant (blister-forming) activity, and extravasation injury (forms deep ulcers). Vinblastine paracrystals may be composed of tightly packed unpolymerized tubulin or microtubules. [13]
Vinblastine is reported to be an effective component of certain chemotherapy regimens, particularly when used with bleomycin and methotrexate in VBM chemotherapy for Stage IA or IIA Hodgkin lymphomas. The inclusion of vinblastine allows for lower doses of bleomycin and reduced overall toxicity with larger resting periods between chemotherapy cycles. [14]
Microtubule-disruptive drugs like vinblastine, colcemid, and nocodazole have been reported to act by two mechanisms. [15] At very low concentrations they suppress microtubule dynamics and at higher concentrations they reduce microtubule polymer mass. Recent findings indicate that they also produce microtubule fragments by stimulating microtubule minus-end detachment from their organizing centers. Dose-response studies further indicate that enhanced microtubule detachment from spindle poles correlate best with cytotoxicity. [16] But research into the mechanism is still ongoing as recent studies also show vinblastine inducing apoptosis that is phase-independent in certain leukemias. [17]
Vinblastine appears to be a peripherally selective drug due to limited brain uptake caused by binding to P-glycoprotein. [18] [19]
Vinblastine may be isolated from the Madagascar Periwinkle ( Catharanthus roseus ), its only known biological producer, [20] along with several of its precursors, catharanthine and vindoline. Extraction is costly and yields of vinblastine and its precursors are low, although procedures for rapid isolation with improved yields avoiding auto-oxidation have been developed. Enantioselective synthesis has been of considerable interest in recent years, as the natural mixture of isomers is not an economical source for the required C16'S, C14'R stereochemistry of biologically active vinblastine. Initially, the approach depends upon an enantioselective Sharpless epoxidation, which sets the stereochemistry at C20. The desired configuration around C16 and C14 can then be fixed during the ensuing steps. In this pathway, vinblastine is constructed by a series of cyclization and coupling reactions which create the required stereochemistry. The overall yield may be as great as 22%, which makes this synthetic approach more attractive than extraction from natural sources, whose overall yield is about 10%. [21] Stereochemistry is controlled through a mixture of chiral agents (Sharpless catalysts), and reaction conditions (temperature, and selected enantiopure starting materials). [22] Due to difficulty of stereochemical restraints in total synthetic processes, other semi-synthetic methods from precursors, catharanthine and vindoline, continue to be developed. [23]
Vinblastine was first isolated by Robert Noble and Charles Thomas Beer at the University of Western Ontario from the Madagascar periwinkle plant. Vinblastine's utility as a chemotherapeutic agent was first suggested by its effect on the body when an extract of the plant was injected in rabbits to study the plant's supposed anti-diabetic effect. (A tea made from the plant was a folk-remedy for diabetes.) The rabbits died from a bacterial infection, due to a decreased number of white blood cells, so it was hypothesized that vinblastine might be effective against cancers of the white blood cells such as lymphoma. [24] It was approved by FDA in 1965. [12]
Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.
Catharanthus is a genus of flowering plants in the family Apocynaceae. Like the genus Vinca, they are known commonly as periwinkles. There are eight known species. Seven are endemic to Madagascar, though one, C. roseus, is widely naturalized around the world. The eighth species, C. pusillus, is native to India and Sri Lanka. The name Catharanthus comes from the Greek for "pure flower".
Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoskeleton. Microtubules function in many essential cellular processes, including mitosis. Tubulin-binding drugs kill cancerous cells by inhibiting microtubule dynamics, which are required for DNA segregation and therefore cell division.
Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's disease, neuroblastoma, and small cell lung cancer among others. It is given intravenously.
Vinca is a genus of flowering plants in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The English name periwinkle is shared with the related genus Catharanthus.
Vinorelbine (NVB), sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer and non-small cell lung cancer. It is given by injection into a vein or by mouth.
Dacarbazine, also known as imidazole carboxamide and sold under the brand name DTIC-Dome, is a chemotherapy medication used in the treatment of melanoma and Hodgkin's lymphoma. For Hodgkin's lymphoma it is often used together with vinblastine, bleomycin, and doxorubicin. It is given by injection into a vein.
Stanford V, is a chemotherapy regimen intended as a first-line treatment for Hodgkin lymphoma. The regimen was developed in 1988, with the objective of maintaining a high remission rate while reducing the incidence of acute and long term toxicity, pulmonary damage, and sterility observed in alternative treatment regimens such as ABVD. The chemical agents used are:
Catharanthus roseus, commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a perennial species of flowering plant in the family Apocynaceae. It is native and endemic to Madagascar, but is grown elsewhere as an ornamental and medicinal plant, and now has a pantropical distribution. It is a source of the drugs vincristine and vinblastine, used to treat cancer. It was formerly included in the genus Vinca as Vinca rosea.
Vinca alkaloids are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived from the periwinkle plant Catharanthus roseus and other vinca plants. They block beta-tubulin polymerization in a dividing cell.
ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, replacing the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs:
Vindesine, also termed Eldisine, is a semisynthetic vinca alkaloid derived from the flowering plant Catharanthus roseus. Like the natural and semisynthetic vinca alkaloids derived from this plant, vindesine is an inhibitor of mitosis that is used as a chemotherapy drug. By inhibiting mitosis, vinedsine blocks the proliferation of cells, particularly the rapidly proliferation cells of certain types of cancer. It is used, generally in combination with other chemotherapeutic drugs, in the treatment of various malignancies such as leukaemia, lymphoma, melanoma, breast cancer, and lung cancer.
Ambovombe-Androy, or just Ambovombe, is a city in the far south of Madagascar, and the capital of the Androy region. Ambovombe has now acquired city status with an officially estimated population in 2018 of 114,230.
Ixabepilone is a pharmaceutical drug developed by Bristol-Myers Squibb as a chemotherapeutic medication for cancer.
A mitotic inhibitor, microtubule inhibitor, or tubulin inhibitor, is a drug that inhibits mitosis, or cell division, and is used in treating cancer, gout, and nail fungus. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow through continuous division that eventually spread through the body (metastasize). Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in cytogenetics, where they stop cell division at a stage where chromosomes can be easily examined.
Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.
Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. In International Nonproprietary Names for MMAE-MAB-conjugates, the name vedotin refers to MMAE plus its linking structure to the antibody. It is a potent antimitotic drug derived from peptides occurring in marine shell-less mollusc Dolabella auricularia called dolastatins which show potent activity in preclinical studies, both in vitro and in vivo, against a range of lymphomas, leukemia and solid tumors. These drugs show potency of up to 200 times that of vinblastine, another antimitotic drug used for Hodgkin lymphoma as well as other types of cancer.
Plant sources of anti-cancer agents are plants, the derivatives of which have been shown to be usable for the treatment or prevention of cancer in humans.
Bis(cyclopentadienyl)titanium(III) chloride, also known as the Nugent–RajanBabu reagent, is the organotitanium compound which exists as a dimer with the formula [(C5H5)2TiCl]2. It is an air sensitive green solid. The complex finds specialized use in synthetic organic chemistry as a single electron reductant.
Moroidin is a biologically active compound found in the plants Dendrocnide moroides and Celosia argentea. It is a peptide composed of eight amino acids, with unusual leucine-tryptophan and tryptophan-histidine cross-links that form its two rings. Moroidin has been shown to be at least one of several bioactive compounds responsible for the painful sting of the Dendrocnide moroides plant. It also has demonstrated anti-mitotic properties, specifically by inhibition of tubulin polymerization. Anti-mitotic activity gives moroidin potential as a chemotherapy drug, and this property combined with its unusual chemical structure has made it a target for organic synthesis.